LONDON — Researchers at the Queen Mary University of London have discovered a novel technique to deprive malignant brain tumor cells of fuel in an effort to stop further development.
If scientists can substantiate the results of recent clinical trials involving humans, pre-clinical studies involving human tissue samples and cells, and studies using mice, it might transform the future of medulloblastoma treatment for certain children.
The most common and highly aggressive brain tumor in children is medulloblastoma. Every year, doctors diagnose around 350 people with this form of cancer in the U.S. The survival rate for individuals who have a benign tumor is 70 percent, however, it is usually deadly if the tumor is malignant.
Cancer-killing chemical lives in plants and animals
The researchers examined inositol hexaphosphate (IP6), a chemical found naturally in nearly all animals and plants. The study demonstrated how it suppresses medulloblastoma and how doctors could pair it with chemotherapy to destroy tumor cells.
“Medulloblastoma occurs in four distinct subgroups (WNT, SHH, G3, and G4). Despite our growing knowledge of the molecular differences between these subgroups, current options are surgery together with radiotherapy and/or chemotherapy for all patients. We desperately need to understand the key molecular events driving tumor growth in each subgroup to design new, less toxic, targeted treatments,” says Professor Silvia Marino, lead researcher from the Brain Tumor Research Center of Excellence, in a university release.
“G4 medulloblastoma is the least understood of all subgroups, despite being the most common and associated with poor prognosis. We have identified a novel way that this type of medulloblastoma is able to adapt its metabolism and grow uncontrollably. Significantly, we have also shown how this energy supply can be blocked. These exciting results bring hope of developing new targeted treatments for patients with this aggressive pediatric brain tumor,” Prof. Marino adds.
What goes wrong in the cells when cancer develops?
Normal, healthy human cells can control their development by turning particular genes on and off when necessary. This process, called epigenetics, differs in cancer cells, resulting in the excess production of certain proteins that lead to the creation and progression of a tumor.
Previous studies have linked epigenetic alterations to the formation of medulloblastoma. Furthermore, BMI1, a protein associated with this process, is present in high quantities in a variety of malignancies, including brain tumors. High amounts of it also appear in the G4 subgroup of medulloblastoma, where it promotes tumor development.
Professor Marino’s team recently revealed that the cells of G4 medulloblastoma lack a protein called CHD7, in addition to having high levels of BMI1. This hallmark of alterations plays a role in the formation of G4 medulloblastoma.
The researchers have since demonstrated that elevated levels of BMI1 allow cancer cells to alter their metabolic activity and proliferate more aggressively. Treatments with inositol hexaphosphate (IP6) can reverse this transformation in the cells. The researchers also discovered that when doctors combine IP6 with chemotherapy treatments – in this study, cisplatin – the capacity to destroy tumor cells in mice increased.
“These very exciting results reveal a new way for epigenetics to control metabolism within tumor cells. Clinical trials are now required to test the efficacy of combining IP6 with chemotherapy to treat G4 medulloblastoma, offering promise to a particularly vulnerable group of patients,” says Hugh Adams, who is head of stakeholder relations at Brain Tumor Research.
“It is great news and brings some much-needed hope for the future. There is still some way to go but we hope that a clinical trial could be up and running in the near future. Brain tumors kill more children and adults under the age of 40 yet, historically, just 1% of the national cancer spend has been allocated to this devastating disease. Brain Tumor Research is determined to change this,” Adams adds.
Turning tragedy into triumph
In November 2017, Peter Gardiner of Aston Clinton lost his 13-year-old son to medulloblastoma. May marked the six-year anniversary of his diagnosis.
“I can only describe our experience as a long hell. Firstly, Ollie was diagnosed, then he went through surgery and extensive treatment. When we were told there were no further options for him in the UK, we crowdfunded nearly $680,000 so he could have immunotherapy in Germany. It was our only hope and, sadly, it didn’t work,” Gardiner says.
Ollie’s family graciously contributed the remaining funds raised to Brain Tumor Research, which is supporting post-doctoral scientist Sara Badodi, who works with Professor Marino.
“We were overwhelmed by the support of friends, family, and strangers who stood by us in our hour of need and came together to help us do the very best we could for our son. It means the world to think that, because of him and the love people showed to us, others might not have to go through what we did,” Gardiner adds.
This findings appear in the journal Nature Communications.